The Dienolate [2,3]-Wittig Rearrangement – Diastereoselective Synthesis of Highly Functionalized Tertiary Alcohols

Hiersemann, Martin; Lauterbach, Christa; Pollex, A.

doi:10.1002/(sici)1099-0690(199911)1999:11<2713::aid-ejoc2713>3.0.co;2-e

Cited by 15 publications

(11 citation statements)

References 53 publications

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“…Furthermore, when treated with an appropriate base a-allyloxy-substituted a,b-unsaturated esters 1 can be transformed to the corresponding dienolates which undergo a dienolate [2,3]-Wittig rearrangement to 3-alkoxycarbonyl-3-hydroxy-substituted 1,5-hexadienes. 4 These compounds are substrates for a domino 3-oxy-Cope rearrangement/type II carbonyl ene reaction affording substituted carbocycles (Scheme 2). 5…”

Section: Methodsmentioning

confidence: 99%

“…Even as a mixture of double bond isomers, the esters 1 have already been utilized as starting materials for diastereoselective sequential pericyclic reactions and for a metal catalyzed Claisen rearrangement. 3,4,5 Further work aimed at exploiting the synthetic potential of the 2-alkoxycarbonyl-substituted allyl vinyl ethers 1 is currently under way.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of α-Allyloxy-Substituted α,β-Unsaturated Esters via Aldol Condensation. Convenient Access of Highly Substituted Allyl Vinyl Ethers

Hiersemann¹

2000

Synthesis

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a-Allyloxy-substituted a,b-unsaturated esters 1a-r have been prepared in 5 steps from commercially available starting materials. The key sequence of the synthesis is an aldol addition between an a-allyloxy-substituted ester 2a-i and an aldehyde R 1 CHO followed by mesylation and DBU mediated elimination to afford the 2-alkoxycarbonyl-substituted allyl vinyl ethers 1a-r. The E/Z ratio of the newly generated vinyl ether double bond is apparently determined by the steric bulk of the vinyl ether double bond substituent R 1 . Z:E ratios from 3:2-9:1 were obtained.Without doubt, sigmatropic rearrangements create one of the most important classes of synthetic transformations.Several striking examples have proven the utility of sigmatropic rearrangements for the stereoselective synthesis of organic compounds. 1 In an ongoing effort to further increase the synthetic efficiency, much work is devoted to extend the scope of classical sigmatropic rearrangements. 2 In this regard, we are engaged in a research program which focuses on the development of metal catalyzed Claisen rearrangements and pericyclic domino reactions which are triggered by a dienolate [2,3]-Wittig rearrangement. The starting materials for both processes are a-allyloxy-substituted a,b-unsaturated esters 1.Particularly, we were able to show that the 2-alkoxycarbonyl-substituted allyl vinyl ether 1f can be transformed to an a-keto ester diastereoselectively employing a combination of Pd(II)-catalysis and thermal reaction conditions (Scheme 1). 3 Scheme 1Furthermore, when treated with an appropriate base a-allyloxy-substituted a,b-unsaturated esters 1 can be transformed to the corresponding dienolates which undergo a dienolate [2,3]-Wittig rearrangement to 3-alkoxycarbonyl-3-hydroxy-substituted 1,5-hexadienes. 4 These compounds are substrates for a domino 3-oxy-Cope rearrangement/type II carbonyl ene reaction affording substituted carbocycles (Scheme 2). 5 Scheme 2Finally, we have recently established first examples for a domino ester dienolate [2,3]-Wittig/anionic 3-oxy Cope rearrangement to afford the corresponding a-keto esters (Scheme 3). 6 Scheme 3Obviously, it was indispensable to develop a reliable, flexible and efficient synthetic access to a-allyloxy-subEt CO 2 R O n-Pr Et n-Pr CO 2 R O 5 % PdCl 2 (PhCN) 2 toluene 60 °C, 3 h 150 °C 3 h 90 % anti:syn 95:5 1f, R= CH 2 CH 2 OCH 3 Z:E= 67:33 OH CO 2 i-Pr OH CO 2 i-Pr Ph Ph O Ph CO 2 i-Pr O Ph O Oi-Pr Li O CO 2 i-Pr Ph LDA, THF -78 °C to 25 °C 89 % toluene 200 °C, 19 h sealed tube 85 % [3,3] ene [2,3] O O Oi-Pr CO 2 i-Pr O LDA, THF -78 °C to 25 °C 84 % 1h Downloaded by: University of Pittsburgh. Copyrighted material. 1280 M. Hiersemann PAPER Synthesis 2000, No. 9, 1279-1290 ISSN 0039-7881 © Thieme Stuttgart · New Yorkstituted a,b-unsaturated esters 1 to be in the position to study the scope and limitations of the newly developed synthetic processes. At the outset, an aldol condensation strategy seemed to be an ideal approach with respect to synthetic convergence and substrate availability (Scheme 4). Sche...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis of α-Allyloxy-Substituted α,β-Unsaturated Esters via Aldol Condensation. Convenient Access of Highly Substituted Allyl Vinyl Ethers

Hiersemann¹

2000

Synthesis

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“…Since we failed to mesylate the tertiary hydroxy group, thionyl chloride in pyridine was used for the elimination leading to a mixture of the a,b-and b,g-unsaturated esters 10 and 11. 15,17,18 The non-conjugated, b,gunsaturated ester 10 was preferentially formed under the reaction conditions depicted in Scheme 7. The regioisomers 10 and 11 may be separated by careful flash chromatography.…”

Section: Substrate Synthesismentioning

confidence: 99%

“…18 1,5-Hexadienes 9f,g were also made accessible by this procedure. 18 The rearrangement proceeded at low temperature in the absence of donor solvents or metal salts. As mentioned above, the (-)-menthyl-induced diastereoselectivity was disappointingly low.…”

Section: The Ester Dienolate [23]-wittig Rearrangementmentioning

confidence: 99%

“…19 We adapted those stereochemical models for the ester dienolate [2,3]-Wittig rearrangement and formulated the qualitative model depicted in Scheme 15. 18 Starting from the dienolate E-or Z-12, the (E)-lk and the (Z)-ul transition states are destabilized by an eclipsed arrangement of the substituents on the two trigonal carbons which approach each other during C-C-bond formation. On the other hand, the (E)-ul and the (Z)-lk transition states are characterized by a gauche arrangement of the corresponding substituents.…”

Section: R 5ementioning

confidence: 99%

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The Ester Dienolate [2,3]-WittigRearrangement - Development, Opportunities, andLimitations

Hiersemann¹,

Abraham²,

Pollex³

2003

Synlett

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T h e E s t e r D i e n o l a t e [ 2 , 3 ] -W i t t i g R e a r r a n g e m e n t Abstract: The account summarizes the development of the ester dienolate [2,3]-Wittig rearrangement as a versatile synthetic tool for the construction of highly substituted 3-alkoxycarbonyl-3-hydroxysubstituted 1,5-hexadienes. Furthermore, the account provides an insight into a novel sequential pericyclic reaction employing the 1,5-hexadienes accessible through the ester dienolate [2,3]-Wittig rearrangement.

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Sequencing Pericyclic Reactions: The Ester Dienolate [2,3]-Wittig/Oxy-Cope Rearrangement/Carbonyl Ene Reaction, a New Access to Substituted Carbocycles

Hiersemann

2001

Eur. J. Org. Chem.

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The sequential ester dienolate [2,3]-Wittig/oxy-Cope rearrangement/carbonyl ene reaction has been investigated. Acyclic α,β-unsaturated α-allyloxy-substituted esters 1a−j were transformed into cyclopentane-or cyclohexanecarboxylates 6a−f and 7a−7d. This study presents a domino ester dienolate [2,3]-Wittig/oxy-Cope rearrangement or a domino oxy-Cope rearrangement/carbonyl ene reaction, depending on the substrate structure. The thermal intramolecular type-

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The Dienolate [2,3]-Wittig Rearrangement – Diastereoselective Synthesis of Highly Functionalized Tertiary Alcohols

Cited by 15 publications

References 53 publications

Synthesis of α-Allyloxy-Substituted α,β-Unsaturated Esters via Aldol Condensation. Convenient Access of Highly Substituted Allyl Vinyl Ethers

Synthesis of α-Allyloxy-Substituted α,β-Unsaturated Esters via Aldol Condensation. Convenient Access of Highly Substituted Allyl Vinyl Ethers

The Ester Dienolate [2,3]-WittigRearrangement - Development, Opportunities, andLimitations

Sequencing Pericyclic Reactions: The Ester Dienolate [2,3]-Wittig/Oxy-Cope Rearrangement/Carbonyl Ene Reaction, a New Access to Substituted Carbocycles

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